Friday, June 1, 2012

Zinc Helps Fight Infant Infections - MedPage Today



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  • Zinc aided antibiotic treatment for serious infection in infants in developing countries.
  • Note that significantly fewer treatment failures occurred in the zinc group compared with the placebo group.

Zinc aided antibiotic treatment for serious infection in infants in developing countries, a randomized controlled trial showed.

Adding oral zinc to standard antibiotics reduced the risk of treatment failure by 40% compared with standard antibiotics alone (P=0.0113), Shinjini Bhatnagar, PhD, of the Translational Health Science and Technology Institute in Gurgaon, India, and colleagues found.

The number needed to treat for probable serious bacterial infection was just 15 for this composite of needing to switch antibiotics within 7 days, intensive care admission, or death within 21 days, they reported online in The Lancet.

If further trials confirm a benefit, "the use of zinc as an adjunct to antibiotic treatment might lead to substantial reductions in infant mortality, particularly in resource-constrained settings where second-line antibiotics and appropriate intensive care might be unavailable," they wrote.

The trial showed a signal for reduced mortality with zinc, with 10 deaths versus 17 in the placebo group for a 43% lower relative risk, although the difference was not statistically significant at P=0.15 and the trial was underpowered to look for such a difference.

The results are promising to fill the need for straightforward and inexpensive treatments to reduce the high proportion of early childhood deaths in low- and middle-income countries, according to an accompanying editorial.

Zinc deficiency is widespread in such areas -- documented in more than 40% of children in the trial -- noted Christa L. Fischer Walker, MHS, PhD, and Robert E. Black, MD, MPH, both of Johns Hopkins School of Public Health in Baltimore.

Zinc syrup or dispersible tablets are already widely available in developing nations as a treatment for diarrhea, the researchers pointed out.

However, replication of the findings is needed before making recommendations for use, Fischer and Walker cautioned.

The trial included 352 infants ages 7 days to 4 months at three hospitals in India with probable serious bacterial infection based on clinical signs and high levels of the inflammatory marker serum C-reactive protein.

"Probable serious bacterial infection is an appropriate clinical diagnosis for this age group, because pneumonia, sepsis, and meningitis are often difficult to distinguish clinically from each other in the first few months of life," the editorial noted. "Thus, a treatment that is effective across the entire range of serious infections in young infants could be implemented in low-level health facilities."

These infants were randomized to double-blind treatment with standard antibiotic treatment plus either placebo or zinc administered as half a 10-mg tablet dissolved in breast milk or distilled water every 12 hours until recovery.

For the primary endpoint, treatment failure rates were 10% with zinc compared with 17% with placebo, for an absolute 7% risk reduction (P=0.0111).

Among the components, need for intensive care occurred in one zinc-treated infant and two in the placebo group, which suggested a halving in that risk, though based on small numbers.

Change of antibiotics occurred equally often between groups for worsening of initial clinical features (5% in both) but less often in the zinc group for persistence of initial clinical features (2% versus 6%). Overall, the difference in risk was of borderline significance.

Recovery time didn't improve with zinc.

Infants with diarrhea appeared to particularly benefit, with a relative risk reduction of 69% compared with placebo (P=0.0009, P=0.0260 for interaction).

That benefit may have stemmed from replenishing zinc stores depleted by loss in stool, Bhatnagar's group suggested.

"Zinc is important for mucosal barrier function and components of innate and adaptive immunity, such as lytic activity of phagocytes and natural killer cells, and expression of cytokines," they noted.

Other potential mechanisms are modulation of inflammatory response and antioxidant properties, the editorial added.

The study was supported by the Department of Biotechnology, Government of India; the European Commission; the Meltzer Foundation; and the Research Council of Norway.

The researchers reported having no conflicts of interest to disclose.

Fischer Walker, and Black reported having no conflicts of interest to disclose.

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